1. Field of the Invention
The present invention relates to novel protein tyrosine kinase (pTK) genes, the proteins encoded by these genes, RNA nucleic acid sequences which hybridize to the genes, antibodies specific for the encoded proteins, chimeras of the proteins and methods of use therefor.
In particular, this application relates to agonist antibodies which are able to activate the tyrosine kinase domain of the receptor pTKs disclosed herein and pTK-immunoglobulin chimeras.
2. Description of Related Art
Transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases are enzymes that catalyze this process. Moreover, many act as growth factor receptors. The c-kit subgroup of receptor tyrosine kinases catalyze the phosphorylation of exogenous substrates, as well as tyrosine residues within their own polypeptide chains (Ullrich et al., Cell 61:203 [1990]). Members of the c-kit subgroup include FLT/FLK (Fetal Liver Kinase), FGF (Fibroblast Growth Factor Receptor) and NGF (Nerve Growth Factor Receptor).
The EPH tyrosine kinase subfamily, Eph, Elk, Eck, Eek, Hek, Hek2, Sek, Ehk-1, Ehk-2, Cek-4 to -10, Tyro 1, 4, 5 and 6, appears to be the largest subfamily of transmembrane tyrosine kinases (Hirai et al., Science 238:1717-1720 [1987]; Letwin et al., Oncogene 3:621-678 [1988]; Lhotak et al., Mol. Cell. Biol. 13:7071-7079 [1993]; Lindberg et al., Mol. Cell. Biol. 10:6316-6324 [1990]; Bohme et al., Oncogene 8:2857-2862 [1993]; and Wicks et al., Proc. Natl. Acad. Sci. USA. 89:1611-1615 [1992]; Pasquale et al. Cell Regulation 2:523-534 [1991]; Sajjadi et al., New Biol. 3:769-778 [1991]; Wicks et al., Proc. Natl. Acad. Sci. USA. 89:1611-1615 [1992]; Lhotak et al., Mol. Cell. Bio. 11:2496-2502 [1991]; Gilardi-Hebenstreit et al., Oncogene 7:2499-2506 [1992]; Lai et al., Neuron 6:691-704 [1991]; Sajjadi et al., Oncogene 8:1807-1813 [1993]; and Maisonpierre et al., Oncogene 8:3277-3288 [1993]).
Additional pTKs and agonist antibodies thereto are needed in order to further study growth and differentiation of cells, for use as therapeutic agents and for diagnostic purposes. Accordingly, it is an object of the present invention to provide novel pTK genes, the proteins encoded thereby, antibodies specific for the encoded proteins, chimeras of the proteins and methods of use thereof.